IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P12882 | P14859 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238760 |
O95243 | P50613 | 0 | phosphorylation | down-regulates activity | 0.2 | The mechanistic basis for the phase-separation of MED1 is not well understood, and we hypothesize that this may be due to the phosphorylation of MED1 by CDK7 in response to growth stimuli or nuclear translocation of steroid hormone receptors, such as AR.|Together, we demonstrate that CDK7 inhibition selectively targets MED1 mediated, AR dependent oncogenic transcriptional amplification, thus representing a potential new approach for the treatment of CRPC. | SIGNOR-279686 |
P00367 | P00533 | 0 | phosphorylation | up-regulates activity | 0.2 | EGFR phosphorylates GDH1 at Y135 and contributes to GDH1 activation.|Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis. | SIGNOR-279706 |
Q13547 | P36952 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.413 | We found that maspin is selectively upregulated in IFIXα-expressing cells and involved in anti-invasive activity of IFIXα. We also present evidence indicating that IFIXα downregulates histone deacetylase 1 (HDAC1), which is possibly involved in the silencing of the maspin gene in human breast cancer cells. To confirm these results, we performed a luciferase assay using a maspin-promoter-luciferase plasmid. The results showed that HDAC1 overexpression suppressed the activity of the maspin promoter (Figure 3C). Therefore, our results suggest that IFIXα enhances maspin expression through the downregulation of HDAC1. | SIGNOR-268494 |
P49841 | P35659 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.437 | These data suggest that the E3 ligase SCFFbxw7-α degrades p-DEK in a GSK-3β–dependent manner.Therefore, the phosphorylation of DEK by GSK-3β is a crucial step to mediate Tpm RNA splicing. | SIGNOR-276303 |
P46734 | Q99759 | 0 | phosphorylation | up-regulates activity | 0.558 | These data indicate that mkk3 is preferentially activated by mekk3, whereas mkk4 is activated both by mekk2 and mekk3. | SIGNOR-48625 |
Q9NR19 | P04062 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276552 |
P49842 | P01111 | 1 | phosphorylation | up-regulates activity | 0.306 | STK19 Phosphorylates NRAS Protein at Serine 89|STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation.| | SIGNOR-264566 |
O43889 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we found that human CREB3 is phosphorylated within its transcription activation domain on serine 46 by protein kinase CK2. However, phosphorylation at serine 46 reduced the stability of CREB3. | SIGNOR-277501 |
O43293 | P40763 | 1 | phosphorylation | up-regulates activity | 0.401 | ZIPK phosphorylated STAT3 on serine 727 (Ser727) and enhanced STAT3 transcriptional activity. | SIGNOR-279702 |
Q16695 | Q15652 | 0 | demethylation | down-regulates activity | 0.2 | We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state. | SIGNOR-265170 |
P31749 | O60346 | 0 | dephosphorylation | down-regulates | 0.76 | Here, we identify a protein_ phosphatase, ph domain leucine-rich repeat protein_ phosphatase_ (phlpp), that specifically_ dephosphorylates_ the hydrophobic motif of_ akt_ (ser473 in akt1), triggering_ apoptosis_ and suppressing_ tumor_ growth. | SIGNOR-252601 |
P11362 | Q02156 | 0 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 779 in fibroblast growth factor receptor 1 and 2 by protein kinase c(epsilon) regulates ras/mitogen-activated protein kinase signaling and neuronal differentiationour findings show that in addition to fgfr tyrosine phosphorylation, the phosphorylation of a conserved serine residue, ser(779), can quantitatively control ras/mapk signaling to promote specific cellular responses. | SIGNOR-201671 |
P07766 | P16333 | 1 | relocalization | up-regulates activity | 0.372 | We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ϵ and results in recruitment of the adaptor protein Nck. | SIGNOR-259934 |
Q13546 | Q13490 | 0 | polyubiquitination | up-regulates activity | 0.768 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272710 |
O43318 | Q9BXM7 | 0 | phosphorylation | up-regulates activity | 0.33 | PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1. | SIGNOR-279644 |
O76064 | P16104 | 1 | ubiquitination | up-regulates | 0.2 | Rnf8 can ubiquitylate histone h2a and h2ax, | SIGNOR-159309 |
P12755 | Q6ZNA4 | 0 | ubiquitination | down-regulates | 0.595 | On tgf-beta treatment, the e3 ubiquitin ligase arkadia mediates degradation of ski in a smad-dependent manner | SIGNOR-178598 |
Q13464 | P17661 | 1 | phosphorylation | down-regulates | 0.316 | The sites phosphorylated by Aurora-B; Thr-7/Ser-13/Ser-38 of GFAP, and Thr-16 of desmin are common with those related to Rho-associated kinase (Rho-kinase), which has been reported to phosphorylate GFAP and desmin at cleavage furrow during cytokinesis. Rho-kinase was found to phosphorylate desmin at Thr-16, Thr-75, and Thr-76 | SIGNOR-100177 |
P06241 | Q16236 | 1 | phosphorylation | down-regulates quantity | 0.4 | Fyn phosphorylates Nrf2 Y568, resulting in nuclear export and degradation of Nrf2.|Fyn phosphorylates Nrf2Y568 resulting in nuclear export and degradation of Nrf2. | SIGNOR-278358 |
P68400 | Q712K3 | 1 | phosphorylation | up-regulates activity | 0.338 | Ck2-dependent phosphorylation of the e2 ubiquitin conjugating enzyme ubc3b induces its interaction with beta-trcp and enhances beta-catenin degradation | SIGNOR-88050 |
P67870 | Q9UGP8 | 1 | phosphorylation | up-regulates activity | 0.2 | Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62. | SIGNOR-265270 |
Q05655 | O00429 | 1 | phosphorylation | up-regulates | 0.2 | Drp1 was specifically phosphorylated in mitosis by cdk1/cyclin b on ser-585. Exogenous expression of unphosphorylated mutant drp1s585a led to reduced mitotic mitochondrial fragmentation. | SIGNOR-153148 |
O15297 | P04637 | 1 | dephosphorylation | down-regulates activity | 0.558 | PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity. PPM1D also dephosphorylates p53 at phospho-Ser 15. PPM1D dephosphorylations are correlated with reduced cellular intra-S and G2/M checkpoint activity in response to DNA damage induced by ultraviolet and ionizing radiation. Thus, a primary function of PPM1D may be to reverse the p53 and Chk1-induced DNA damage and cell cycle checkpoint responses and return the cell to a homeostatic state following completion of DNA repair. | SIGNOR-248319 |
Q13153 | P78545 | 1 | phosphorylation | up-regulates | 0.456 | Phosphorylation-dependent regulation of stability and transforming potential of ets transcriptional factor ese-1 by p21-activated kinase 1. Pak1 selectively phosphorylates ese-1 at ser(207). Intriguingly, pak1 phosphorylation inactive mutant ese1-s207a is more unstable | SIGNOR-154743 |
Q16816 | P10636 | 1 | phosphorylation | down-regulates activity | 0.313 | Muscle phosphorylase kinase phosphorylates Ser237, Ser262, Ser285, Ser305, and Ser352 of human tau. in vitro phosphorylation of tau on Ser262 alone strongly reduced the ability of tau to bind microtubules whereas the phosphorylation of many Ser/Thr-Pro motif sites of tau showed moderate effects on the binding of tau to microtubules | SIGNOR-250285 |
P52655 | P68400 | 0 | phosphorylation | up-regulates activity | 0.379 | We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function. | SIGNOR-250877 |
P17861 | O75460 | 0 | phosphorylation | up-regulates activity | 0.647 | IRE1\u03b1 phosphorylates and activates the XBP1 transcription factor XBP1 via its kinase activity. | SIGNOR-279712 |
P51587 | P53350 | 0 | phosphorylation | down-regulates activity | 0.539 | M phase-specific phosphorylation of brca2 by polo-like kinase 1 correlates with the dissociation of the brca2-p/caf complex.Plk1 interacts with brca2 in vivo, and mutation of ser193, ser205/206, and thr203/207 to ala in br-n1 abolished plk1 phosphorylation, suggesting that brca2 is the substrate of plk1 | SIGNOR-102486 |
Q8IWQ3 | Q9Y484 | 1 | phosphorylation | up-regulates activity | 0.248 | WIPI4 is stimulated by AMPK, NUAK2 and BRSK2. This finding is supported by the results of our kinome screening, which identified AMPK and the AMKP-related kinases NUAK2 and BRSK2, all of which function downstream of LKB1 (ref. 69) and stimulate the localization of WIPI4 to nascent autophagosomes. | SIGNOR-268482 |
Q00535 | O75962 | 1 | phosphorylation | up-regulates activity | 0.2 | Roscovitine inhibits the ability of Trio to activate Rac, and peptides corresponding to the Cdk5 consensus sites in Trio are phosphorylated by Cdk5.|Together, these data suggest that control of the cortical actin cytoskeleton, long known to modulate hormone exocytosis and subsequent endocytosis, involves Cdk5 mediated activation of Trio. | SIGNOR-280220 |
Q14247 | P00519 | 0 | phosphorylation | up-regulates activity | 0.424 | Because phosphorylation by c-Abl augments nmMLCK-cortactin interaction to a greater degree than does pp60src phosphorylation, it is likely that phosphorylation sites on nmMLCK unique to c-Abl (i.e., other than Y464 and Y846) are responsible for this enhanced protein-protein interaction.|Moreover, our data indicate that cortactin is itself rapidly phosphorylated on Y486 by c-Abl in EC after S1P (Figure 9). | SIGNOR-278504 |
P40818 | P56817 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.45 | Accordingly, we reported that BACE1 is ubiquitinated at lysine 501 and that lack of ubiquitination at lysine 501 produces BACE1 stabilization.Our findings demonstrate that USP8 plays a key role in the trafficking and degradation of BACE1 by deubiquitinating lysine 501. | SIGNOR-259101 |
P46527 | P36888 | 0 | phosphorylation | down-regulates activity | 0.29 | FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27 Kip1 in acute myeloid leukemia|P27Kip1 (p27) can prevent cell proliferation by inactivating cyclin-dependent kinases. This function is impaired upon phosphorylation of p27 at tyrosine residue 88. | SIGNOR-269208 |
Q13794 | Q9UBF6 | 0 | ubiquitination | down-regulates activity | 0.39 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271446 |
P49841 | Q9Y5Q3 | 1 | phosphorylation | down-regulates | 0.2 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity. | SIGNOR-159476 |
Q96I25 | P21127 | 0 | phosphorylation | up-regulates activity | 0.207 | However, Clk1 enhanced SPF45 protein expression, but not mRNA expression, whereas inhibition of Clk1 increased SPF45 degradation through a proteasome dependent pathway.|In the present work, we show that Clk1 phosphorylates SPF45 in vitro on eight serine residues, all of which are N-terminal to the RRM domain required for splicing. | SIGNOR-279510 |
P35222 | Q13616 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.598 | These results indicate that the cul1/skp1/beta-trcp complex forms a ubiquitin ligase that mediates the degradation of beta-catenin. | SIGNOR-64499 |
P01106 | P62714 | 0 | dephosphorylation | down-regulates | 0.276 | Phosphorylation at ser-62 by pro-directed kinases (p-k) is a prerequisite for gsk3-dependent phosphorylation of thr-58. This triggers binding of pin1, subsequently protein phosphatase 2a (pp2a)-dependent dephosphorylation of ser-62, and then recruitment of scf-fbw7 to the thr-58-phosphorylated myc. Scf-fbw7 polyubiquitinylates myc (branching through lys-48), leading to its proteasomal degradation. | SIGNOR-149726 |
Q13309 | Q13485 | 1 | ubiquitination | down-regulates | 0.397 | We found that skp2, the f-box component of scfskp2, physically interacted with smad4 at the physiological levels. Several cancer-derived unstable mutants exhibited significantly increased binding to skp2, which led to their increased ubiquitination and accelerated proteolysis. These results suggest an important role for the scfskp2 complex in switching cancer mutants of smad4 to undergo polyubiquitination-dependent degradation. | SIGNOR-127964 |
Q02156 | O14649 | 1 | phosphorylation | down-regulates activity | 0.2 | We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel. | SIGNOR-276431 |
P06493 | P06748 | 1 | phosphorylation | down-regulates activity | 0.518 | However, under the experimental conditions used here, the t199 residue was the most likely candidate to be phosphorylated by cyclin b/cdc2 these results strongly support the concept that the rna binding activity of b23.1 is inactivated by cyclin b/cdc2-mediated phosphorylation. | SIGNOR-89605 |
Q9BV73 | Q96KG9 | 0 | relocalization | down-regulates activity | 0.2 | Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting. | SIGNOR-265497 |
P28482 | Q15366 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.318 | We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B). | SIGNOR-262912 |
P10451 | P09237 | 0 | cleavage | up-regulates activity | 0.706 | In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA. | SIGNOR-253321 |
Q13489 | Q9Y572 | 1 | polyubiquitination | up-regulates activity | 0.647 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272714 |
Q15418 | Q9H6Z4 | 1 | phosphorylation | up-regulates quantity | 0.319 | RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran | SIGNOR-276149 |
Q13153 | P49593 | 0 | dephosphorylation | down-regulates activity | 0.39 | The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family|POPX Can Dephosphorylate and Downregulate PAK| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX. | SIGNOR-248530 |
P19525 | P25963 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.532 | As described for other stimuli, following pIC treatment, PKR phosphorylates the NF-kappa B inhibitor I kappa B alpha at serine 32 before degradation. | SIGNOR-249335 |
P68431 | P49336 | 0 | phosphorylation | down-regulates activity | 0.2 | However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo. | SIGNOR-273171 |
Q96PU5 | Q15858 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.334 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253458 |
P17252 | P49407 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrate that β-arrestin-1 recruitment to the TCR, and bystander TCR and CXCR4 downregulation, are mechanistically mediated by the TCR-triggered PKC-mediated phosphorylation of β-arrestin-1 at Ser163. | SIGNOR-276619 |
P17252 | P18031 | 1 | phosphorylation | up-regulates activity | 0.249 | PKC\u03b1 then phosphorylates and activates endothelial cell protein tyrosine phosphatase 1B (PTP1B) , . | SIGNOR-279257 |
P68400 | O75379 | 1 | phosphorylation | up-regulates | 0.446 | The r-snare vamp4, which contains a dileucine motif, binds to the ap-1 or the ggas. Serine 20 and leucines 25,26 are essential for this binding. Ap-1 association with vamp4 is enhanced when serine 30 is phosphorylated by casein kinase 2. This phosphorylation-dependent modulation of ap-1 binding is mediated by pacs-1 (phosphofurin acidic cluster sorting protein). Ablation of both the dileucine motif and serine 30 results in a dramatic mislocalization of vamp4 in the regulated secretory pathway. | SIGNOR-119090 |
Q12913 | P40198 | 1 | dephosphorylation | down-regulates activity | 0.387 | We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3. | SIGNOR-277091 |
P49840 | O75581 | 1 | phosphorylation | up-regulates activity | 0.632 | Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 | SIGNOR-275398 |
Q96MM3 | Q9NVW2 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.337 | RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. | SIGNOR-269002 |
P04628 | P11308 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression. | SIGNOR-261597 |
Q8TDX7 | P54274 | 1 | phosphorylation | up-regulates activity | 0.342 | Using KR-TRF2 to induce telomeric DNA damage, we found that TRF1 degradation was also exacerbated when ATM was inhibited after damage induction (55.2% of mock treated cells) (XREF_FIG), indicating that the ATM signal pathway is required for Nek7 mediated TRF1 stabilization.|We show that Nek7 phosphorylates TRF1 at Ser114 and in turn maintains stability of the shelterin complex at telomeres. | SIGNOR-278447 |
Q13315 | P20823 | 1 | phosphorylation | up-regulates | 0.256 | Serine 249 phosphorylation by atm protein kinase regulates hepatocyte nuclear factor-1_ transactivation | SIGNOR-205087 |
Q14247 | Q14289 | 0 | phosphorylation | up-regulates activity | 0.365 | In conclusion, these data suggest that Pyk2 phosphorylates cortactin on tyrosine residues Y421, Y466, and Y482.|To confirm the direct and indirect effects of Pyk2 on cortactin phosphorylation, we used cells overexpressing Arg YFP and treated with Pyk2 siRNA or a nonsilencing siRNA. | SIGNOR-278344 |
Q15418 | P50549 | 1 | phosphorylation | up-regulates activity | 0.35 | Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation. | SIGNOR-249163 |
Q92993 | P35790 | 1 | acetylation | up-regulates activity | 0.2 | Glucose deprivation induces the binding of choline kinase α2 (CHKα2) to lipid droplets, followed by a continuous PTMs to promote lipolysis of lipid droplets, which are in turn mediated by AMPK-dependent CHKα2 Serine 279 phosphorylation and KAT5-dependent CHKα2 Lysine 247 acetylation. | SIGNOR-267648 |
O14965 | Q93073 | 1 | phosphorylation | up-regulates quantity | 0.2 | To explore the underlying mechanisms, we found that SLAN, a potential tumor suppressor, served as a substrate of Aurora-A and knockdown of SLAN induced immature cytokinesis. Aurora-A phosphorylates SLAN at T573 under the help of the scaffold protein 14-3-3η. Intriguingly, SLAN T573D or T573E inactivated and T573A activated the key cytokinesis regulator RhoA. | SIGNOR-273547 |
P31941 | Q13617 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.251 | Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation|Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner. | SIGNOR-261325 |
Q92905 | O15111 | 0 | phosphorylation | down-regulates activity | 0.325 | Overexpression of IKKalpha or IKKbeta leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro. | SIGNOR-275507 |
P30533 | Q9NYY3 | 0 | phosphorylation | up-regulates activity | 0.3 | Inhibition of Ras and activation of Rap by Plk2.|Plk2 phosphorylation of Ras and Rap regulators controls surface AMPARs. | SIGNOR-279476 |
O43379 | P24941 | 1 | relocalization | up-regulates activity | 0.244 | Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. | SIGNOR-271726 |
P38936 | Q7Z419 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.359 | P53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1. Here we report the isolation of a novel transcriptional target of p53, designated p53RFP (p53-inducible RING-finger protein), whose product has E3 ubiquitin ligase activity. Its expression was negatively correlated to that of p21(WAF1) protein; p53RFP is likely to play a role in the regulation of this protein, probably through interaction with, and ubiquitination of, p21(WAF1). | SIGNOR-271478 |
Q13315 | P16220 | 1 | phosphorylation | down-regulates | 0.522 | Individual ala substitutions at thr-100, ser-111, or ser-121 inhibited atm-catalyzed phosphate incorporationatm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp) | SIGNOR-124051 |
P07858 | P02818 | 1 | cleavage | down-regulates quantity by destabilization | 0.33 | This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42. | SIGNOR-256318 |
Q6IQ22 | Q6YBV0 | 1 | relocalization | down-regulates quantity by destabilization | 0.445 | We also found that Rab12 promotes constitutive degradation of PAT4 (proton‐coupled amino‐acid transporter 4|Rab12 regulates lysosomal localization or degradation of amino‐acid transporters. | SIGNOR-264763 |
Q9HCX4 | Q13976 | 0 | phosphorylation | up-regulates activity | 0.2 | In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. These data indicate that cGK-Iα interacts with and phosphorylates TRPC7, contributing to the quick and accurate regulation of calcium influx and CREB phosphorylation. | SIGNOR-263184 |
O43464 | Q9BXM7 | 0 | phosphorylation | up-regulates | 0.607 | Htra2 is phosphorylated on activation of the p38 pathway, occurring in a pink1-dependent mannerwe suggest that pink1-dependent phosphorylation of htra2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress. | SIGNOR-158052 |
P36873 | Q13422 | 1 | dephosphorylation | up-regulates | 0.329 | Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway | SIGNOR-174865 |
O43521 | P06493 | 0 | phosphorylation | up-regulates activity | 0.404 | Furthermore, active recombinant Cdk1/cyclin B1 phosphorylates BimEL and BimL in vitro and Serine 44 on BimL has been identified as a Cdk1 phosphorylation site. Collectively, these results suggest that Cdk1/cyclin B1-dependent hyper-phosphorylation of Bim during prolonged mitotic arrest is an important cell death signal. | SIGNOR-267985 |
Q9ULW0 | P24941 | 0 | phosphorylation | down-regulates activity | 0.294 | In this study, we characterize the phosphorylation of threonine 72 (Thr(72)) in human TPX2, a residue highly conserved across species. We find that Cdk1/2 phosphorylate TPX2 in vitro and in vivo. |Endogenous TPX2 phosphorylated at Thr(72) does not associate with the mitotic spindle. Furthermore, ectopic GFP-TPX2 T72A preferentially concentrates on the spindle | SIGNOR-265099 |
Q92993 | P49841 | 0 | phosphorylation | up-regulates | 0.367 | We demonstrate that gsk-3 phosphorylates serine 86 of the p53-acetyltransferase tip60. A tip60(s86a) mutant was less active to induce p53 k120 acetylation, histone 4 acetylation, and expression of puma | SIGNOR-174049 |
P04629 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.476 | Here, we identify SHP-1 as a phosphotyrosine phosphatase that negatively regulates TrkA. SHP-1 formed complexes with TrkA at Y490, and dephosphorylated it at Y674/675. | SIGNOR-248468 |
P45983 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.296 | Instead, we found that rock activates jnk, which then phosphorylates c-jun and atf2 when bound to the c-jun promoter. | SIGNOR-123717 |
P31749 | Q9Y4P1 | 1 | phosphorylation | up-regulates activity | 0.31 | In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity. | SIGNOR-275834 |
Q9HBA0 | Q96J02 | 0 | ubiquitination | down-regulates activity | 0.377 | AIP4 ubiquitin ligase is involved in the ubiquitination of both TRPV4 and TRPC4.Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane. | SIGNOR-272625 |
P06493 | O94782 | 1 | phosphorylation | up-regulates activity | 0.371 | In this study, we show that Ser313 phosphorylation in USP1 is required for its interaction with UAF1 and for the stimulation of USP1's activity. We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1. | SIGNOR-276423 |
Q15173 | P10415 | 1 | dephosphorylation | down-regulates | 0.323 | Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site. | SIGNOR-181559 |
P63279 | O14503 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.326 | Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9. | SIGNOR-272579 |
P25054 | P04264 | 0 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of this central repeat region of APC significantly enhances its affinity for β-catenin. When the repeats are phosphorylated by the cooperative action of CK1 and GSK3β, the binding interaction is significantly altered and enhanced. | SIGNOR-251879 |
Q86X55 | Q02078 | 1 | methylation | up-regulates | 0.387 | The first evidence alluding to a role of PRMTs in mediating skeletal muscle plasticity, specifically myogenesis, arose from the identification of CARM1 as a glucocorticoid receptor-interacting protein 1 (GRIP1) binding protein. (Chen et al., 2000). Here, GRIP1 and MEF2 were co-expressed in the nucleus during skeletal muscle differentiation. These initial findings led to an investigation that revealed that this methyltransferase was responsible for coactivating the transcription of myocyte enhancer factor-2C (MEF2C) via GRIP1 | SIGNOR-255964 |
Q86Y07 | P04637 | 1 | phosphorylation | up-regulates activity | 0.383 | Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells.|Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation. | SIGNOR-280162 |
O43524 | Q13627 | 0 | phosphorylation | down-regulates | 0.359 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity phosphorylation of foxos by akt, ikk, erk, ck1, cdk2, and dyrk1a universally leads to foxo's inhibition. | SIGNOR-183674 |
Q15438 | P06241 | 0 | phosphorylation | up-regulates activity | 0.394 | Fyn directly binds, phosphorylates, and activates cytohesin-1. | SIGNOR-280015 |
Q96T60 | Q13315 | 0 | phosphorylation | up-regulates | 0.462 | We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro. | SIGNOR-176008 |
Q9Y243 | O60346 | 0 | dephosphorylation | down-regulates activity | 0.648 | The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells. | SIGNOR-248330 |
P46108 | Q05397 | 1 | phosphorylation | up-regulates activity | 0.733 | Tyrosine phosphorylation FAK was strictly dependent upon c-Crk II expression | Crk-inducible FAK tyrosine phosphorylation was completely abrogated by co-expression with R38K Crk (lane 2), and decreased by co-expression with W170K Crk (lane 3), indicating that the SH2 domain of c-Crk is absolutely essential for this effect. In contrast, mutants in the C-terminus of Crk that include Y222F c-Crk, which abrogates the c-Abl phosphorylation site, and W276K Crk, which mutates the C-terminal SH3 domain, modestly increased FAK activation compared to wild-type c-Crk II. | SIGNOR-250777 |
Q6JBY9 | P49137 | 0 | phosphorylation | down-regulates activity | 0.477 | Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ. | SIGNOR-263080 |
P41597 | O60674 | 0 | phosphorylation | up-regulates activity | 0.605 | JAK2 phosphorylates CCR2 at the Tyr139 position and promotes JAK2/STAT3 complex association to the receptor. | SIGNOR-251345 |
O60260 | P37840 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R). | SIGNOR-249705 |
Q9Y6C9 | P55957 | 1 | relocalization | up-regulates | 0.303 | Mtch2/mimp (mitochondrial carrier homologue 2/met-induced mitochondrial protein), a novel truncated bid (tbid)-interacting protein, is a surface-exposed outer mitochondrial membrane protein that facilitates the recruitment of tbid to mitochondria | SIGNOR-165081 |
Q04759 | Q8IVH8 | 0 | phosphorylation | up-regulates | 0.38 | We report that the kinase glk (map4k3) directly activated pkc-? During tcr signaling. | SIGNOR-176744 |
P06239 | Q16539 | 1 | phosphorylation | up-regulates activity | 0.475 | Lck, Fyn, and Zap70 activate p38 even in the absence of Tyr182 phosphorylation.p38 is a substrate for Fyn, Lck and Zap70.Thus, T cell Src family kinases and Zap70 activate p38 by phosphorylating Tyr323. | SIGNOR-276029 |
Q15208 | P17612 | 0 | phosphorylation | down-regulates activity | 0.295 | GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress. | SIGNOR-276390 |
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